Biofilm-targeted liposomal curcumin delivery system for anti-caries therapy

Dental caries, driven by acidogenic biofilms, remains a major global health challenge. Current chemical treatments, such as chlorhexidine and fluoride, can disrupt oral microbial homeostasis and cause adverse effects, including tooth discoloration, dentin hypersensitivity, and taste disturbances. Curcumin, a natural photosensitizer, exhibits antibacterial activity and favorable biocompatibility, however, its clinical application is limited by poor stability, low aqueous solubility, and restricted biofilm penetration. There is an urgent need to develop innovative therapeutic strategies to enhance curcumin transport into acidic cariogenic biofilms.

We developed a pH-responsive liposomal delivery system (Cur/DCPA-H₂O) engineered to penetrate acidic cariogenic biofilms and enhance curcumin transport. The physicochemical characterization of Cur/DCPA-H₂O was performed using a UV-1800 spectrophotometer, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Biocompatibility was assessed by Cell Counting Kit-8 (CCK-8) assays, hemolysis tests, and Live/Dead cell staining. The antibacterial efficacy in vitro and ex vivo was evaluated using colony-forming unit (CFU) counting, scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and crystal violet (CV) staining. An in vivo caries model was established to assess the therapeutic efficacy of Cur/DCPA-H₂O, using micro-computed tomography (micro-CT), Keyes' scoring, and 16S rRNA sequencing.

The liposomes exploit charge reversal to interact with representative caries-associated bacteria (Streptococcus mutans and the early colonizer Streptococcus sanguinis), enabling deep biofilm penetration. Upon light irradiation, Cur/DCPA-H₂O was observed to generate reactive oxygen species (ROS), which may contribute to partial disruption of the biofilm matrix and reduced bacterial viability in vitro. In a rat caries model, treatment with Cur/DCPA-H₂O under light irradiation reduced caries severity and decreased lesion depth by approximately 50%. It also shifted the oral microbiome composition toward a less dysbiotic profile, as confirmed by 16S rRNA sequencing.

This study demonstrates that a biofilm-targeted, pH responsive liposomal curcumin delivery system may provide a safe and effective strategy for caries prevention, highlighting the potential of natural therapeutics to modulate pathogenic biofilms with limited impact on the overall microbial community.